We propose to develop synthetic methodology which would be useful in syntheses of chemotherapeutics and to investigate model reactions of important biological processes. In both areas the processes to be studied are based on previous discoveries of new and/or novel chemistry in our laboratories. The use of alpha-heteroatom dipole stabilized carbanions in a synthetic sequence which provides electrophilic substitution adjacent to the heteroatoms of alchohols, thiols, and amines via the metalated esters, thioesters, and amides will be investigated. This methodology should provide alpha-lithioalcohol, alpha-lithiothiol, and alpha-lithioamine synthetic equivalents. The role of dipole stabilized carbanions in enzymatic decarboxylations will be evaluated in model studies. Extension of the use of secondary and tertiary amides, which we have shown to be the most powerful activities for ortho metalation, in regiospecific syntheses substituted of heteroaromatic and alicyclic systems is to be studied. The use of heterophilic additions to give synthetic equivalent of electrophilic oxygen and nitrogen at the oxidation level of alcohols and amines will be investigated.